Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance

ABSTRACT Candida species are a major cause of life-threatening bloodstream infections worldwide. Although Candida albicans is responsible for the vast majority of infections, the clinical relevance of other Candida species has also emerged over the last twenty years. This shift might be due in part...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Csaba Papp, Katica Kocsis, Renáta Tóth, László Bodai, Jesse R. Willis, Ewa Ksiezopolska, Nancy E. Lozoya-Pérez, Csaba Vágvölgyi, Hector Mora Montes, Toni Gabaldón, Joshua D. Nosanchuk, Attila Gácser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Candida parapsilosis echinocandins microevolution virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/922ca16d97be49b1beb1863a635e647b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:922ca16d97be49b1beb1863a635e647b
record_format	dspace
spelling	oai:doaj.org-article:922ca16d97be49b1beb1863a635e647b2021-11-15T15:22:21ZEchinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance10.1128/mSphere.00547-182379-5042https://doaj.org/article/922ca16d97be49b1beb1863a635e647b2018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00547-18https://doaj.org/toc/2379-5042ABSTRACT Candida species are a major cause of life-threatening bloodstream infections worldwide. Although Candida albicans is responsible for the vast majority of infections, the clinical relevance of other Candida species has also emerged over the last twenty years. This shift might be due in part to changes in clinical guidelines, as echinocandins became the first line of therapeutics for the treatment. Candida parapsilosis is an emerging non-albicans Candida species that exhibits lower susceptibility levels to these drugs. Candida species frequently display resistance to echinocandins, and the mechanism for this is well-known in C. albicans and Candida glabrata, where it is mediated by amino acid substitutions at defined locations of the β-1,3-glucan synthase, Fks1p. In C. parapsilosis isolates, Fks1p harbors an intrinsic amino acid change at position 660 of the hot spot 1 (HS1) region, which is thought to be responsible for the high MIC values. Less is known about acquired substitutions in this species. In this study, we used directed evolution experiments to generate C. parapsilosis strains with acquired resistance to caspofungin, anidulafungin, and micafungin. We showed that cross-resistance was dependent on the type of echinocandin used to generate the evolved strains. During their characterization, all mutant strains showed attenuated virulence in vivo and also displayed alterations in the exposure of inner cell wall components. The evolved strains harbored 251 amino acid changes, including three in the HS1, HS2, and HS3 regions of Fks1p. Altogether, our results demonstrate a direct connection between acquired antifungal resistance and virulence of C. parapsilosis. IMPORTANCE Candida parapsilosis is an opportunistic fungal pathogen with the ability to cause infections in immunocompromised patients. Echinocandins are the currently recommended first line of treatment for all Candida species. Resistance of Candida albicans to this drug type is well characterized. C. parapsilosis strains have the lowest in vitro susceptibility to echinocandins; however, patients with such infections typically respond well to echinocandin therapy. There is little knowledge of acquired resistance in C. parapsilosis and its consequences on other characteristics such as virulence properties. In this study, we aimed to dissect how acquired echinocandin resistance influences the pathogenicity of C. parapsilosis and to develop explanations for why echinocandins are clinically effective in the setting of acquired resistance.Csaba PappKatica KocsisRenáta TóthLászló BodaiJesse R. WillisEwa KsiezopolskaNancy E. Lozoya-PérezCsaba VágvölgyiHector Mora MontesToni GabaldónJoshua D. NosanchukAttila GácserAmerican Society for MicrobiologyarticleCandida parapsilosisechinocandinsmicroevolutionvirulenceMicrobiologyQR1-502ENmSphere, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida parapsilosis echinocandins microevolution virulence Microbiology QR1-502
spellingShingle	Candida parapsilosis echinocandins microevolution virulence Microbiology QR1-502 Csaba Papp Katica Kocsis Renáta Tóth László Bodai Jesse R. Willis Ewa Ksiezopolska Nancy E. Lozoya-Pérez Csaba Vágvölgyi Hector Mora Montes Toni Gabaldón Joshua D. Nosanchuk Attila Gácser Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance
description	ABSTRACT Candida species are a major cause of life-threatening bloodstream infections worldwide. Although Candida albicans is responsible for the vast majority of infections, the clinical relevance of other Candida species has also emerged over the last twenty years. This shift might be due in part to changes in clinical guidelines, as echinocandins became the first line of therapeutics for the treatment. Candida parapsilosis is an emerging non-albicans Candida species that exhibits lower susceptibility levels to these drugs. Candida species frequently display resistance to echinocandins, and the mechanism for this is well-known in C. albicans and Candida glabrata, where it is mediated by amino acid substitutions at defined locations of the β-1,3-glucan synthase, Fks1p. In C. parapsilosis isolates, Fks1p harbors an intrinsic amino acid change at position 660 of the hot spot 1 (HS1) region, which is thought to be responsible for the high MIC values. Less is known about acquired substitutions in this species. In this study, we used directed evolution experiments to generate C. parapsilosis strains with acquired resistance to caspofungin, anidulafungin, and micafungin. We showed that cross-resistance was dependent on the type of echinocandin used to generate the evolved strains. During their characterization, all mutant strains showed attenuated virulence in vivo and also displayed alterations in the exposure of inner cell wall components. The evolved strains harbored 251 amino acid changes, including three in the HS1, HS2, and HS3 regions of Fks1p. Altogether, our results demonstrate a direct connection between acquired antifungal resistance and virulence of C. parapsilosis. IMPORTANCE Candida parapsilosis is an opportunistic fungal pathogen with the ability to cause infections in immunocompromised patients. Echinocandins are the currently recommended first line of treatment for all Candida species. Resistance of Candida albicans to this drug type is well characterized. C. parapsilosis strains have the lowest in vitro susceptibility to echinocandins; however, patients with such infections typically respond well to echinocandin therapy. There is little knowledge of acquired resistance in C. parapsilosis and its consequences on other characteristics such as virulence properties. In this study, we aimed to dissect how acquired echinocandin resistance influences the pathogenicity of C. parapsilosis and to develop explanations for why echinocandins are clinically effective in the setting of acquired resistance.
format	article
author	Csaba Papp Katica Kocsis Renáta Tóth László Bodai Jesse R. Willis Ewa Ksiezopolska Nancy E. Lozoya-Pérez Csaba Vágvölgyi Hector Mora Montes Toni Gabaldón Joshua D. Nosanchuk Attila Gácser
author_facet	Csaba Papp Katica Kocsis Renáta Tóth László Bodai Jesse R. Willis Ewa Ksiezopolska Nancy E. Lozoya-Pérez Csaba Vágvölgyi Hector Mora Montes Toni Gabaldón Joshua D. Nosanchuk Attila Gácser
author_sort	Csaba Papp
title	Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance
title_short	Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance
title_full	Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance
title_fullStr	Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance
title_full_unstemmed	Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance
title_sort	echinocandin-induced microevolution of <named-content content-type="genus-species">candida parapsilosis</named-content> influences virulence and abiotic stress tolerance
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/922ca16d97be49b1beb1863a635e647b
work_keys_str_mv	AT csabapapp echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT katicakocsis echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT renatatoth echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT laszlobodai echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT jesserwillis echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT ewaksiezopolska echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT nancyelozoyaperez echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT csabavagvolgyi echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT hectormoramontes echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT tonigabaldon echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT joshuadnosanchuk echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance AT attilagacser echinocandininducedmicroevolutionofnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontentinfluencesvirulenceandabioticstresstolerance
_version_	1718428018197659648

Echinocandin-Induced Microevolution of <named-content content-type="genus-species">Candida parapsilosis</named-content> Influences Virulence and Abiotic Stress Tolerance

Ejemplares similares